An EU-funded study has uncovered data that suggests a change in the behaviour of certain genes - the unit of heredity in a living organism - could be involved in precipitating epilepsy. By gaining a better understanding of exactly how the brain works, the EpiTarGene project aims to open the door to potential new therapies and novel drugs.

Epilepsy is the most common chronic disorder of the central nervous system and in many cases is resistant to drugs. The EpiTarGene project has made some significant steps in helping scientists understand why conditions such as epilepsy may come about. This breakthrough could lead to treatments that could eventually improve the lives of millions of epileptic sufferers.

Understanding brain 'plasticity'
Epilepsy is a brain disorder in which a person suffers from repeated seizures over time. Seizures are episodes of disturbed brain activity that can cause dramatic and sudden changes in behaviour. This chronic neurological disorder affects between 1% and 3% of the human population, and many sufferers are resistant to current anti-epileptic drugs on the market.

One of the reasons the brain remains such a challenge for neuroscientists is due to its 'plasticity'  the fact that it changes throughout an individual's life. Neuronal plasticity  the ability of neurons to change their biochemical, structural or functional properties in response to new experiences  plays a crucial role in the brain.

Neurons process and transmit information through electrical and chemical signals via 'synapses' (structures that allow neurons to pass on information). Scientists now know that neuronal plasticity is fundamental for learning and memory. Some abnormal forms of plasticity however may explain the development of brain disorders, such as epilepsy.

One of the mechanisms regulating plasticity is the modulation of gene expression, the process by which information from a gene is used. This activity is controlled in turn by regulatory proteins, called 'transcription factors'. One of the main goals of the EpiTarGene project has therefore been to understand the molecular basis of abnormal plasticity observed in epilepsy, and to identify the genes involved in this process.

So far, the project has uncovered clues as to the circumstances that could lead to malfunctions in the brain, causing disorders.

Solving the puzzle
"This project is based on the hypothesis that many genes that encode effector proteins (proteins that regulate biological activity) in aberrant (or abnormal) plasticity can be transcriptionally modulated via one of the major regulatory proteins in the brain, SRF (Serum Response Factor)," explains project coordinator Dr Katarzyna Kalita.

"So far, with the use of global genomic screening we have succeeded in finding a group of genes controlled by SRF in response to seizures."

The team is currently working on the characterisation of these effector proteins in order to fully address their role in neuronal plasticity. This work could prove to be crucial in advancing our understanding of epilepsy, and helping scientists to develop strategies to repair injured neuronal circuitries. The project also has the potential to increase European competitiveness through the development of patents and the eventual delivery of novel drugs to the worldwide market.

"Finding new effector proteins will allow us to dissect molecular and cellular mechanisms underlying synapse remodelling that occur also in epilepsy," says Dr Kalita. "We believe that our data will have an impact on current understanding of the pathogenesis of epilepsy, as well as influence the development of new therapeutic opportunities by selectively targeting aberrant plasticity-related effectors."

Moreover, the results obtained so far provide scientists with exciting new starting points for research into chronic neurological disorders such as epilepsy, migraine and Parkinson's disease.